ABC transporter



ATP Binding Cassette (ABC) Transporters are ATP-dependent membrane proteins critical for most aspects of cell physiology, including the uptake of nutrients (importers) and elimination of waste products and energy generation (exporters) which are predominantly expressed in excretory organs, such as the liver, intestine, blood-brain barrier, blood-testes barrier, placenta, and kidney. There are many ABC Transporters in organisms, for instance, there are 28 in Saccharomyces,58 in Caenorhabditis, 51 in Drosophila,129 in Arabadopsis,and the 69 ABC transporters in E. coli account for almost 5% of its genomic coding capacity. ABC transporter protein translocates substrates across membranes. It contains a Solute Binding Domain (SBD). CFTR (Cystic Fibrosis Transmembrane Regulator) translocates chloride and  thiocyanate. It contains a nucleotide binding domain (NBD). Mutations in CFTR lead to Cystic Fibrosis. In humans the ABC transporters are classified into subfamilies, i.e. ABCB6 is ABC subfamily B member 6. The images at the left and at the right correspond to one representative ABC transporter, i.e. the crystal structure of B12 Bacterial ABC Transporter (1l7v).

Function
ABC Transporters has two main functionality acting either as exporters or importers. ABC Exporters release bound drugs to the extracellular environment, while ABC Importers accept substrate molecules from their relevant substrate-binding proteins. For instance the Vitamin B12 transporter BtuCD (PDB 1l7v) is a binding protein-dependent ABC transporter system that uses the power of ATP hydrolysis to pump vitamin B12 into the cytoplasm of E. coli.

ABC Exporters Use ATP to drive import and export functions providing multidrug resistance. In eukaryoles, for instance, ABC Transporters are problematic because they export therapeutic drugs such as those used in chemotherapy regimens, which must be changed frequently to avoid the rejection of the drugs.

To achieve export, ABC transporters require a minimum of four domains. Two transmembrane domains (TMDs) form the ligand binding sites and provide specificity, and two NBDs bind and hydrolyze ATP to drive the trans-location of the bound ligand. The NBDs, but not the TMDs, are homologous throughout the family and have several characteristic motifs including the Walker A and B motifs common to many nucleotide binding proteins and others like the ABC signature, stacking aromatic D, H, and Q loops, which are unique to the family.

3D Structures of ABC transporter
Update June 2011

ABC amino acids transporters
3g41 - CpABC arginine transporter, soluble domain (mutant) – Chlamydia pneumoniae

3n26 - CpABC arginine transporter, soluble domain

3lkb - TtABC branched amino acids transporter (mutant)+valine – Thermus thermophilus

3l49 - ABC ribose transporter – Rhodobacter sphaeroides

3k4u - ABC transporter + lysine – Wolinella succinogenes

3i6v - SpABC amino acids transporter + lysine – Silicibacter pomeroyi

3h5l - SpABC branched-chain amino acids transporter

1g9x, 1g6h, 1gaj - ABC branched-chain amino acids transporter – Methanocaldococcus jannaschii

3i09 - ABC branched amino acids transporter – Burkholderia mallei

3hv1 - ABC polar amino acids transporter SBD – Streptococcus thermophilus

3c41 - GsABC amino acids transporter +AMP-PNP – Geobacillus stearothermophilus

3c4j - GsABC amino acids transporter +ATPgS

2pvu - GsABC amino acids transporter (mutant)+lysine

2q2a - GsABC amino acids transporter (mutant)+arginine

2q2c - GsABC amino acids transporter (mutant)+histidine

2olj - EcABC amino acid transporter+ADP/Mg – Escherichia coli

2olk - EcABC amino acid transporter+ADP-beta-S

2ouk - EcABC amino acid transporter+sulfate

2qsw - EfABC methionine transporter C-terminal – Enterococcus faecalis

3o6p - EfABC amino acids transporter

2qrr - ABC methionine transporter soluble domain – Vibrio parahaemolyticus

3i5o, 1vr5 - TmABC oligopeptides transporter - Thermotoga maritime

3ip5, 3ipa – AtABC alanine transporter – Agrobacterium tumefaciens

3ip6 – AtABC proline transporter

3ip7 – AtABC valine transporter

3ipc – AtABC leucine transporter

3ip9 – AtABC amino acid transporter+GABA

ABC sugar transporters
2vk2 - EcABC galactofuranose transporter +galactofuranose

2w7y - SpABC sugar transporter+A-trisaccaride – Streptococcus pneumoniae

2i58 - SpABC sugar transporter+raffinose

2hq0, 2heu, 2hfb - SpABC sugar transporter

3g1w - ABC sugar transporter – Bacillus halodurans

2z8d - BlABC lacto-N-biose transporter SBD+lacto-N-biose – Bifidobacterium longum

2z8e - BlABC lacto-N-biose transporter SBD+galacto-N-biose

2z8f - BlABC lacto-N-biose transporter SBD+lacto-N-tetraose

3c6q - TmABC sugar transporter (mutant)+beta-xylopyranose

2yyz, 2qvc, 2h3h, 2hpg, 2ghb - TmABC sugar transporter

2fn9 - TmABC sugar transporter (mutant)

2o7i - TmABC sugar transporter+cellobiose

2gha, 2fnc - TmABC sugar transporter+maltotriose

2fn8 - TmABC sugar transporter+ribose

1vci, 1v43 - PhABC sugar transporter – Pyrococcus horikoshii

1oxx, 1oxs, 1oxt, 1oxu, 1oxv - ABC glucose transporter (mutant) – Sulfolobus solfataricus

ABC metal transporters
3hh8 - ABC metal transporter – Streptococcus pyogenes

3gfo - ABC cobalt transporter – Clostridium perfringens

3lr1 - ABC tungstate transporter – Geobacter sulfurreducens

3lhs, 3li2 - SaABC OpuAC ferrichrome transporter fragment+Staphyloferrin A - Staphylococcus aureus

3mwf, 3mwg - SaABC siderophore transporter +Staphyloferrin B

3g9q - BsABC ferrichrome transporter

3be5, 3be6 - EcABC iron transporter

3d31 - MaABC sulfate/molybdate transporter – Methanosarcina acetivorans

3cfx - MaABC sulfate/molybdate transporter + WO4

3cfz - MjABC sulfate/molybdate transporter + WO4

3cg1 - ABC sulfate/molybdate transporter + WO4 – Pyrococcus furiosus

3cg3 - PhABC sulfate/molybdate transporter + WO4

2etv - TmABC iron transporter

2ogw - EcABC zinc transporter

2xh8 - SeABC zinc transporter (mutant) – Salmonella enterica

2xqv - SeABC zinc transporter + Zn

2xy4 - SeABC zinc transporter

2ov3, 2ov1, 1pq4 - SsABC zinc transporter – Synechocystis

2onk - AfABC molybdate/tungstate transporter+Mo/W binding protein – Archaeoglobus fulgidus

2onr - AfABC molybdate/tungstate transporter+Mo

2ons - AfABC molybdate/tungstate transporter+W

ABC multidrug transporters
2onj - SaABC multidrug transporter+AMP-PNP

2hyd - SaABC multidrug transporter

1mv5 - LlABC multidrug transporter ATP binding domain – Lactococcus lactis

ABC choline transporters
3hcq - SmABC choline transporter (mutant) – Sinorhizobium meliloti

2rin - SmABC choline transporter (mutant)+acetylcholine

2reg - SmABC choline transporter (mutant)+choline

2rej, 2rf1 - SmABC choline transporter (mutant)

3o66 – SaABC choline transporter

ABC alpha-hemolysin transporters
2pmk - EcABC alpha-hemolysin transporter+TNP-ADP

2ff7 - EcABC alpha-hemolysin transporter+ADP

2ffa, 2ffb - EcABC alpha-hemolysin transporter (mutant)+ADP

2fgj, 2fgk, 2xef - EcABC alpha-hemolysin transporter (mutant)+ATP

3b5j - EcABC alpha-hemolysin transporter (mutant)+TNP-ADP

ABC various compounds transporters
2v84 - ABC spermidine/putrescine transporter – Treponema pallidum

2qi9 - EcABC vitamin B12 transporter+BtuD+BtuF

1l7v - EcABC vitamin B12 transporter+BtuD

1twy - ABC phosphate transporter – Vibrio cholerae

3l6g, 3l6h – LlABC OpuAC betaine transporter SBD

2zzv - TtABC solute transporter+lactate+Ca

2zzw - TtABC solute transporter+lactate+Zn

2zzx - TtABC solute transporter+lactate

3gfv - BsABC petrobactin transporter – Bacillus subtilis

hABC transporters subfamilies
3nh6 – hABCB6 NBD

3nhb – hABCB6 NBD+ADP

3nh9 – hABCB6 NBD+ATP

3nha – hABCB6 NBD+ATP+Mg

ABC unspecified transporters
3lvu - SpABC transporter SBD

2ihy - SaABC transporter ATPase subunit

3eaf - ABC transporter SBD – Aeropyrum pernix

3c9h - AtABC transporter – Agrobacterium tumefaciens

1vpl, 1ji0 - TmABC transporter

2pcj, 2pcl - ABC transporter – Aquifex aeolicus

3rpw - ABC transporter – Rhodopseudomonas palustris

CFTR
3gd7 – hCFTR/malK+N6-phenylethyl-ATP

2pze, 2pzf, 2pzg – hCFTR NBD1

2bbo, 2bbs, 2bbt - hCFTR NBD1 (mutant)

1xmi, 2xmj - hCFTR NBD1 (mutant)+ATP

1xf9, 2xfa - mCFTR NBD1 (mutant) - mouse

1q3h - mCFTR NBD1+AMPPNP

1r0w - mCFTR NBD1

1r0x, 1r0z, 1r10 - mCFTR NBD1+ATP

1r0y - mCFTR NBD1+ADP

1ckw, 1ckx, 1cky, 1ckz – CFTR F508 region - NMR